| Project/Area Number |
15K08077
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Nara Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
野口 隆一 奈良県立医科大学, 医学部附属病院, 研究員 (30423908)
吉治 仁志 奈良県立医科大学, 医学部, 教授 (40336855)
北出 光輝 奈良県立医科大学, 医学部, 学内講師 (40526795)
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| Co-Investigator(Renkei-kenkyūsha) |
Moriya Kei 奈良県立医科大学, 医学部, 講師 (40526852)
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| Research Collaborator |
Nishimura Norihisa 奈良県立医科大学, 医学部附属病院, 研究員
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 胆汁酸 / 肝線維化 / 肝癌 / OCT1 / FXR / farnesoid X receptor / ウルソデオキシコール酸 |
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| Outline of Final Research Achievements |
We aimed to investigate the combined effect of FXR agonist and angiotensin II type 1 receptor blocker (ARB) on hepatic fibrogenesis in rat model of NASH.The in vitro and in vivo effects of an FXR agonist (INT747 at 30 mg/kg/day) and an ARB (Losartan: 30 mg/kg/day) on hepatic fibrogenesis were evaluated.In PS-administered OLETF rats, INT747 and losartan had potent inhibitory effects on hepatic fibrogenesis with suppression of HSC activation and expression of transforming growth factor (TGF)-β1 and TLR4. INT747 decreased intestinal permeability by ameliorating zonula occuludens-1 (ZO-1) disruption, whereas losartan directly suppressed the regulation of Ac-HSC. The in vitro and in vivo inhibitory effects of INT747 and losartan on TGF-β1 and TLR4 mRNA expression in Ac-HSC were almost in parallel. Losartan directly inhibited the regulation of Ac-HSC. Combined treatment may represent a promising novel approach for NASH.
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